Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents.
The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac-superior mesenteric ganglionectomy (CGX). Irrespective of the operational procedure, rimonabant (10mg/kg) effectively reduced standard chow as well as palatable diet (ensure) intake. In conclusion, the data clearly demonstrate that neither vagal gut afferents, nor gut afferents traveling via the sympathetic nervous system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia.
Madsen
Andreas N
AN
Rheoscience A/S, 2610 Rødovre, Denmark. anm@rheoscience.com
Jelsing
Jacob
J
van de Wall
Esther H E M
EH
Vrang
Niels
N
Larsen
Philip J
PJ
Schwartz
Gary J
GJ
D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000503:physiopathology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000502:physiology*; D015171:Ganglionectomy / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D013266:Stilbamidines / Q000378:metabolism; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology* / Q000601:surgery
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D010880:Piperidines; D011720:Pyrazoles; D013266:Stilbamidines; D000077285:Rimonabant